Use of manometric temperature measurement (MTM) and SMART freeze dryer technology for development of an optimized...

This report provides, for the first time, a summary of experiments using SMART Freeze Dryer technology during a 9 month testing period. A minimum ice sublimation area of about 300 cm(2) for the laboratory freeze dryer, with a chamber volume 107.5 L, was found consistent with data obtained during previous experiments with a smaller freeze dryer (52 L). Good reproducibility was found for cycle design with different type of excipients, formulations, and vials used. SMART primary drying end point estimates were accurate in the majority of the experiments, but showed an over prediction of primary cycle time when the product did not fully achieve steady state conditions before the first MTM measurement was performed. Product resistance data for 5% sucrose mixtures at varying fill depths were very reproducible. Product temperature determined by SMART was typically in good agreement with thermocouple data through about 50% of primary drying time, with significant deviations occurring near the end of primary drying, as expected, but showing a bias much earlier in primary drying for high solid content formulations (16.6% Pfizer product) and polyvinylpyrrolidone (40 kDa) likely due to water "re-adsorption" by the amorphous product during the MTM test.